title: Human primary bone sarcomas contain CD133+ cancer stem cells displaying high tumorigenicity in vivo.
abstract: This study aimed to identify, isolate, and characterize cancer stem cells from human primary sarcomas. We performed cytometric analyses for stemness and differentiation antigens, including CD29, CD34, CD44, CD90, CD117, and CD133, on 21 human primary sarcomas on the day of surgery. From sarcoma biopsies, we obtained 2 chondrosarcoma-stabilized cell lines and 2 osteosarcoma stabilized cell lines, on which sphere formation, side population profile, stemness gene expression, and in vivo and in vitro assays were performed. All samples expressed the CD133, CD44, and CD29 markers. Therefore, we selected a CD133(+) subpopulation from stabilized cell lines that displayed the capacity to grow as sarcospheres able to initiate and sustain tumor growth in nonobese diabetic/severe combined (NOD/SCID) mice, to express stemness genes, including OCT3/4, Nanog, Sox2, and Nestin, and to differentiate into mesenchymal lineages, such as osteoblasts and adipocytes. Our findings show the existence of cancer stem cells in human primary bone sarcomas and highlight CD133 as a pivotal marker for identification of these cells. This may be of primary importance in the development of new therapeutic strategies and new prognostic procedures against these highly aggressive and metastatic tumors.
authors.affiliation: Department of Experimental Medicine, Section of Histology and Embryology, 5 via L. Armanni, Second University of Naples, 80138 Naples, Italy.
authors.forename: Virginia
authors.initials: V
authors.lastname: Tirino
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Desiderio
authors.forename: Francesca
authors.initials: F
authors.lastname: Paino
authors.forename: Alfredo
authors.initials: A
authors.lastname: De Rosa
authors.forename: Federica
authors.initials: F
authors.lastname: Papaccio
authors.forename: Flavio
authors.initials: F
authors.lastname: Fazioli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pirozzi
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Papaccio
mesh_terms: D000071916:AC133 Antigen; D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001859:Bone Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002813:Chondrosarcoma / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D012516:Osteosarcoma / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse